Generally, preparing pharmaceuticals involves the extraction of the desired pharmaceutical from a liquid medium, typically a fermentation mixture. Extraction is necessary because the liquid medium may contain not only the desired pharmaceutical, but may also contain contaminants and impurities such as microorganisms, enzymes and other undesirable components. Typically, this process is carried out in industrial bioreactors through batch production or in continuous production.
Extraction of the desired pharmaceutical is typically accomplished in a multi-step process. After or shortly before adjusting the pH up or down as necessary, a solvent is added to the liquid medium, typically an organic phase such as amyl acetate, methyl ethyl ketone, amyl alcohol, butyl alcohol, benzyl alcohol or the like. The solvent is added to extract the desired pharmaceutical from the liquid medium to the organic phase. The liquid medium is then separated from the organic phase. However, this separation may be difficult to achieve as the liquid medium and organic phase often form an emulsion. Over time, the liquid medium and organic phase slowly separate themselves. More often, however, the addition of a demulsifier is desirable to encourage or speed up the separation of the phases.
After separation of the solvent phase and the liquid medium, the solvent phase is generally made up of the desired pharmaceutical, solvent, as well as trace amounts of impurities or contaminants. Conversely, the liquid medium is generally made the remaining impurities, contaminants and other undesirable components. There may also be trace amounts of the desired pharmaceutical remaining/dissolved in the liquid medium.
In addition, the solvent phase may be purified and decontaminated after separation from the water phase by, for example, the addition of purified water or passing the solvent through active carbon.
In a further step, the desired pharmaceutical can then be extracted from the solvent and into a water phase. One way this can be accomplished is by a re-adjustment of the pH of the mix. It is sometimes desirable to isolate a particular phase to more effectively isolate the pharmaceutical (e.g., precipitation of the active from water more easily achieved), among other reasons. Further, separation of the new water and solvent emulsion can be achieved through the similar aforementioned process. Excess solvent or water can be evaporated off, depending on the phase in which the pharmaceutical is maintained.